Studies will be carried out to determine the features of the steroid molecule that are required to inhibit sterol synthesis and to depress the level of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultures of mouse liver cells and mouse fibroblasts. The effects of qualitative and quantitative alterations in the sterol concentration of cells and cell membranes upon cell growth and upon various parameters of membrane function will be investigated. Binding of an inhibitory sterol (25-hydroxycholesterol) and a noninhibitory sterol (cholesterol) to cytoplasmic proteins of normal and malignant cells will be investigated. The effects of inhibitory sterols (25-hydroxycholesterol and 7-ketocholesterol) upon serum cholesterol levels, rates of cholesterol synthesis in normal and malignant cells, and upon growth of tumors and normal tissues will be studied in vivo. BIBLIOGRAPHIC REFERENCES: Kandutsch, A. A., and H. W. Chen. 1975. Regulation of sterol synthesis in cultured cells by oxygenated derivatives of cholesterol. J. Cell Physiol. 84:415-424. Chen, H. W., H-J. Heiniger, and A. A. Kandutsch. 1975. Relationship between sterol synthesis and DNA synthesis in phytohemagglutinin-stimulated mouse lymphocytes. Proc. Nat. Acad. Sci. 72:1950-1954.